Toxin-Antitoxin Modules Are Pliable Switches Activated by Multiple Protease Pathways

• Published in: Toxins Vol. 8; no. 7; p. 214
• Main Authors: Muthuramalingam, Meenakumari, White, John C, Bourne, Christina R
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 09.07.2016; MDPI AG
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Antitoxins - metabolism; Bacteria - drug effects; Bacteria - enzymology; Bacteria - growth & development; Bacteria - pathogenicity; bacterial physiology; Bacterial Toxins - metabolism; cellular proteases; Endopeptidase Clp - metabolism; environmental adaptation; Enzyme Activation; Host-Pathogen Interactions; Humans; persister cells; phenotypic changes; post-segregational killing; protease adaptors; Protease La - metabolism; Proteolysis; Review; Signal Transduction - drug effects; toxin-antitoxin; bacterial physiology; cellular proteases; phenotypic changes; post-segregational killing; toxin-antitoxin; environmental adaptation; protease adaptors; persister cells
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins8070214

Toxin-antitoxin (TA) modules are bacterial regulatory switches that facilitate conflicting outcomes for cells by promoting a pro-survival phenotypic adaptation and/or by directly mediating cell death, all through the toxin activity upon degradation of antitoxin. Intensive study has revealed specific details of TA module functions, but significant gaps remain about the molecular details of activation via antitoxin degradation used by different bacteria and in different environments. This review summarizes the current state of knowledge about the interaction of antitoxins with cellular proteases Lon and ClpP to mediate TA module activation. An understanding of these processes can answer long-standing questions regarding stochastic versus specific activation of TA modules and provide insight into the potential for manipulation of TA modules to alter bacterial growth.